Institut Curie, PSL Research University, CNRS, UMR 144, Structure and Membrane Compartments, Paris F-75005, France.
Institut Curie, PSL Research University, CNRS, UMR 144, Molecular Mechanisms of Intracellular Transport, Paris F-75005, France.
Nat Commun. 2017 Jun 13;8:15835. doi: 10.1038/ncomms15835.
Exocytic carriers convey neo-synthesized components from the Golgi apparatus to the cell surface. While the release and anterograde movement of Golgi-derived vesicles require the small GTPase RAB6, its effector ELKS promotes the targeting and docking of secretory vesicles to particular areas of the plasma membrane. Here, we show that specialized cell types exploit and divert the secretory pathway towards lysosome related organelles. In cultured melanocytes, the secretory route relies on RAB6 and ELKS to directly transport and dock Golgi-derived carriers to melanosomes. By delivering specific cargos, such as MART-1 and TYRP2/ DCT, the RAB6/ELKS-dependent secretory pathway controls the formation and maturation of melanosomes but also pigment synthesis. In addition, pigmentation defects are observed in RAB6 KO mice. Our data together reveal for the first time that the secretory pathway can be directed towards intracellular organelles of endosomal origin to ensure their biogenesis and function.
胞吐载体将新合成的成分从高尔基体运送到细胞表面。虽然高尔基体衍生小泡的释放和逆行运动需要小分子 GTPase RAB6，但它的效应因子 ELKS 促进了分泌小泡靶向并停靠到质膜的特定区域。在这里，我们表明，特化的细胞类型利用并改变了通向溶酶体相关细胞器的分泌途径。在培养的黑素细胞中，分泌途径依赖于 RAB6 和 ELKS 将高尔基体衍生的载体直接运输并停靠到黑素体上。通过输送特定的 cargo，如 MART-1 和 TYRP2/DCT，RAB6/ELKS 依赖性分泌途径控制黑素体的形成和成熟，但也控制色素合成。此外，在 RAB6 KO 小鼠中观察到色素沉着缺陷。我们的数据首次共同揭示，分泌途径可以被引导到内体起源的细胞内细胞器，以确保它们的生物发生和功能。
